[Lethal and mutagenic effects of tritium incorporated into position 8 of the purines in phage lambda DNA and the role of the Fpg protein].

The lethal and mutagenic effects of the decay of 3H incorporated in phage lambda DNA as 8-3H-adenosine and 8-3H-guanosine were studied, using the DNA of 8-3H-adenine as a labeled DNA precursor. A transmutation component of 3H decay is involved in formation of 8-oxoguanine (8-oxo-G) and 8-oxoadenine (8-oxo-A) residues in phage DNA. The efficiency of phage inactivation (the number of lethal lesions per one tritium decay in the phage genome) for 3H decay in position 8 of purines was the same as that measured in positions 5 and 6 of pyrimidines (alpha = 0.14 +/- 0.01) and virtually did not depend on the fpg-1::kan mutation in the host gene encoding the Fpg protein (formamidepyrimidine-DNA-glycosylase). The efficiency of the mutagenic effect of 3H-purines Em (frequency of c mutations per one 3H decay in the phage genome) was (2.9 +/- 0.3) x 10(-5) in the fpg+ host and (4.6 +/- 0.4) x 10(-5) in the fpg-host. This means that the Fpg protein excised approximately 40% of premutational DNA lesions (probably, 8-oxo-G residues). Induction of the mutagenic SOS system by UV light caused a 1.5-fold increase in the frequency of c mutations induced by 8-3H-purines in fpg+ cells over that in fpg-cells. This suggests that apurinic AP sites produced after the excision of 8-oxo-G by the Fpg protein are substrates for mutagenic SOS repair.